System for characterizing a cornea and obtaining an opthalmic lens

ABSTRACT

A system for determining the shape of a cornea of an eye illuminates at least one of the interior surface, the posterior surface, and the interior region of the eye with infrared light of a wavelength that can generate fluorescent light from the portion of the cornea illuminated. The generated fluorescent light is then detected. A step of illuminating can comprise focusing the infrared light in a plurality of different planes substantially perpendicular to the optical axis of the eye. From the detected light it is possible to create a map of at least a portion of the interior surface, at least a portion of the posterior surface, and/or portion of the interior region of the cornea. Clarity of vision can be determined by generating autofluorescence from proteins in the pigment epithelial cells of the retina.

CROSS-REFERENCES

This application claims the benefit of the following U.S. provisionalapplication Ser. Nos. 61/209,362 filed Mar. 4, 2009; 61/209,363 filedMar. 4, 2009; 61/181,420 filed May 27, 2009; 61/181,519 filed May 27,2009; and 61/181,525 filed May 27, 2009. These United States provisionalapplications are incorporated herein by reference. To the extent thefollowing description is inconsistent with the disclosures of theprovisional applications, the following description controls.

BACKGROUND

A variety of systems are known for characterizing a cornea, and usinginformation from the characterization to model an ophthalmic lens. Seefor example U.S. Pat. Nos. 6,413,276; 6,511,180; 6,626,535; and7,241,311

A difficulty with known systems for characterizing the cornea is thatproperties of the human cornea can be affected by the amount of waterpresent at the time of measurement. Thus, for example, an ophthalmiclens designed for a patient, where the patient's cornea wascharacterized when the patient had a dry eye condition, may not besuitable for the patient when the patient's eye is adequately hydrated.

Another problem with conventional systems is the internal structure ofthe cornea usually is not considered. It is believed that the focusingeffect of the cornea is achieved by the anterior surface of the cornea,the posterior surface of the cornea, and the interior structure of thecornea, each contributing about 80%, 10%, and 10%, respectively. Thisfailure to consider the internal structure of the cornea, and in someinstances failure to consider the shape of the posterior surface of thecornea, can result in a lens that provides unsatisfactory vision.

Accordingly, there is a need for an improved system for characterizing acornea for the purpose of obtaining ophthalmic lenses for placement inthe human eye. It is also desirable that the system permit analysis ofeffectiveness of a placed lens in focusing light on the retina.

The invention also includes a system for determining the clarity ofvision of a patient to ascertain the effectiveness of an implanted lensor other ophthalmic modification provided to a patient. According tothis method, the eye of the patient is illuminated with a scanning lightof a wavelength that generates fluorescent light at the retina andclarity of the image generated by the fluorescent light is detected suchas with a photodetector. Fluorescent light is generated by proteins inthe pigment epithelial cells of the retina as well as photoreceptors ofthe retina. Then the path length of the scanning light is adjusted toincrease the clarity of the image generated by the fluorescent light.Typically the scanning light has a wavelength of from 750 to about 800nm, and preferably about 780 nm.

SUMMARY

The present invention provides a system that meets this need. The systemincludes a method and apparatus for determining the shape of the corneaof an eye, where the cornea has an anterior surface, a posteriorsurface, and an interior region between the anterior and posteriorsurfaces. The method relies upon generation of fluorescent light by thecornea, unlike prior art techniques, where reflectance of incident lightis used for determining the cornea shape. According to the method, atleast one of the anterior surface, the posterior surface and theinterior region of the eye is illuminated with infrared light of awavelength that can generate fluorescent light from the portion of thecornea illuminated. The generated fluorescent light is detected. Thedetected fluorescence can be used to generate a map of the anteriorsurface, posterior surface, and/or internal region of the cornea. By“anterior surface” there is meant a surface that faces outwardly in theeye. A “posterior surface” faces rearwardly toward the retina.

For example, in the case of the anterior region of the cornea, theoptical path length at a plurality of locations in the interior regionis determined. The presence of generated blue light from the interiorregion indicates the presence of collagen lamellae in the cornea.

Preferably the step of illuminating comprises focusing the infraredlight in a plurality of different planes substantially perpendicular tothe optical axis of the eye. The planes can intersect the anteriorsurface of cornea, the posterior surface of cornea, and/or the interiorregion of the cornea.

The present invention also includes apparatus for performing thismethod. A preferred apparatus comprises a laser for illuminating aselected portion of the cornea with infrared light of a wavelength thatcan generate fluorescent light from the portion of the corneailluminated; focusing means such as focusing lenses for focusing thelight in the selected portion of the cornea; and a detector, such as aphotodiode detector, for detecting the generated fluorescent light.

The invention also includes a system for determining the clarity ofvision of a patient to ascertain the effectiveness of an implanted lensor other ophthalmic modification provided to a patient. According tothis method, the eye of the patient is illuminated with a scanning lightof a wavelength that generates fluorescent light at the retina and theclarity of the image generated by the fluorescent light is detected suchas with a photodetector. Fluorescent light is generated by proteins inthe pigment epithelial cells as well as photoreceptors of the retina.Then the path length of the scanning light is adjusted to increase theclarity of the image generated by the fluorescent light. Typically thescanning light has a wavelength of from 750 to about 800 nm, andpreferably about 780 nm. The term “clarity of vision” refers to theability of a subject to distinguish two images differing in brightness(white is 100% bright and black is 0% bright). The less that the twoimages differ in contrast (relative brightness) where the subject canperceive the difference, the higher the subject's clarity of vision.

DRAWINGS

These and other features, aspects, and advantages of the presentinvention will become better understood with regard to the followingdescription, appended claims, and accompanying drawings where:

FIG. 1 is a schematic drawing of the method of the present inventionbeing used with a pseudophakic eye;

FIG. 2 is a graphical presentation of the presence of sphericalaberration of the crystalline lens of the human eye, and in a post-LASIKeye;

FIG. 3 is a schematic presentation of a route of calculation todetermine clarity of a retinal image;

FIG. 4 is a graphical visualization of the mathematical procedure ofconvolution which can be employed in a computing method to determineclarity of vision;

FIG. 5 is a side cross sectional view showing the stress straindistribution in a loaded cornea as the result of Finite Element Modeling(FEM);

FIG. 6 is a schematic drawing depicting the physical processes of secondharmonic generation imaging (SHGi) and two photon excited fluorescenceimaging (TPEFi);

FIG. 7 schematically shows the major components of a two-photonmicroscope/opthalmoscope that can be employed in the present invention;

FIG. 8 is an overview of SHG-imaging of collagen tissue structures;

FIG. 9 sketches the micromorphometry of the cornea;

FIG. 10 shows a schematic arrangement for generating a composite corneamap over a field of view that resembles the size of a customizedintraocular lens (C-IPSM); and

FIG. 11 is a schematic view of a system for detecting the clarity ofimages achieved with an implanted intraocular lenses.

DESCRIPTION

Overview

A system for determining the topography of the cornea, including thetopography of the anterior and posterior surfaces and interior regionsof the cornea, includes measurement and simulation procedures thatprovide values for the refractive index distribution inside the cornea.Statistical distributions and results of finite element modeling of thestress/strain relationship inside the cornea can be employed.

The apparatus used can be a two-photon microscope to obtain a pluralityof measurements with high spatial resolution. Each individual beam usedin the apparatus can have a unique optical path length. The processes ofSecond Harmonic Generation imaging (SHGi) and Two Photon ExcitedFluorescence imaging (TPEFi) are employed. By using a plurality ofpixelized data that are generated from these measurements, a detailedspatial distribution of the refractive properties of the cornea can beevaluated for the purpose of fabricating an intraocular lens that canprecisely compensate for detected aberrations.

The system also includes techniques for determining the effectiveness ofa lens in the eye, i.e., a quality control technique.

Characterizing the Cornea

Referring initially to FIG. 1, a system for determining the refractiveproperties of an implanted lens, such as a customized intraocular lens,is shown in a schematic drawing, and is generally designated 10. Aplurality of optical rays 40 are transmitted through a pseudophakic eye,implanted with a customized intraocular lens 20, providing localcorrections to the optical path lengths of the individual optical rayswith high spatial resolution. These optical rays are directed throughthe pseudophakic eye to form an image on the retina 30. The plurality ofindividual beams 40 are characterized by the fact that each beam has aunique optical path length. Specifically, each optical path length isindicative of the refraction that was experienced by its respectiveindividual beam during transit of the individual beam through the eye.Next, the optical path lengths of the individual beams are collectivelyused by a computer to create a digitized image on the retina of the eye.The plurality of optical rays 40 is transmitted in sequence through theanterior surface 12 of the cornea 14, the interior region 13 of thecornea 14, the posterior surface 16 of the cornea 14, and a customizedintraocular lens, having an anterior surface layer 22, and is brought toa focused image on the retina 30. A method for forming the lens 20 isdescribed in my co-pending application Ser. No. 12/717,886, filed onMar. 4, 2010, entitled “System for Forming and Modifying Lenses andLenses Formed Thereby”, which is incorporated herein by reference.

In the upper part of the plurality of optical rays 40, three neighboringrays 42, 44, and 46 are depicted, symbolizing a local zone in the zonalapproach. Typically, in ray tracing calculations of highest spatialresolution, tens of millions of rays are evaluated with regard to theiroptical path lengths in the human eye. For calculation purposes, areference plane 18, close to the natural pupil of the pseudophakic eye,is selected, towards which the optical path lengths of the individualbeams are normalized. In particular, the propagation of an individualoptical ray from the pupil plane 18 to the anterior surface 22 of thecustomized intraocular lens 20 can be evaluated as exp(i×(2π/λ)×n(x,y)×z(x,y)), where exp resembles the exponential function,i denotes the imaginary unit number, π amounts to approximately 3.14, λdenotes the wavelength of the optical ray, n(x,y) describes the localrefractive index and z(x,y) the physical distance at the transverselocation with coordinates x and y from the pupil plane 18. Anyinaccuracy of the positioning of the customized intraocular lens(C-IPSM) 20 during lens implantation with regard to axial or lateralposition or tilt can be expressed by a profile of physical lengthsz(x,y) and can be compensated for by in-vivo fine-tuning of the surfacelayer 22 with an optical technique, as described in my aforementionedcopending application Ser. No. 12/717,886, filed on Mar. 4, 2010,entitled “System for Forming and Modifying Lenses and Lenses FormedThereby,” which is incorporated herein by reference.

FIG. 2 is a graphical presentation of the presence of one particularoptical aberration of the human eye, e.g. spherical aberration, in anormal eye (e.g. crystalline lens) and in a post-LASIK eye (e.g.reshaped cornea), visualizing the induction of spherical aberration in apost-LASIK eye 60. In the upper part of FIG. 2, the situation in anormal eye 50 is exemplified. The eyeball 52 contains a cornea 56, alens 54 and a retina 58. Typically, for a pupil diameter of 6 mm, anamount of spherical aberration 59 of approximately one wavelength λ,corresponding to 0.5 μm, is introduced, mainly associated with theperipheral shape of the crystalline lens. In the lower part of FIG. 2,for the case of a post-LASIK eye 60, which underwent a myopia correctionprocedure, the introduction of a considerable amount of sphericalaberration is demonstrated. The eyeball 62 exhibits a cornea 66, a lens64 and a retina 68. Typically, an amount of spherical aberration ofapproximately ten wavelengths (10λ), corresponding to 5 is encountered,mainly associated with the edges of the centrally flattened cornea.

FIG. 3 is a schematic presentation of a route of calculation 70 fordetermining the necessary refractive effect of an implanted lens. Amanifold of optical rays 72 is transformed into a pupil function 74which can be visualized as the spatial distribution of the path lengths76 and can be expressed as the mathematical function 78: P(x,y)=P(x,y)exp(ikW(x,y)), where P(x,y) is the amplitude and exp(ikW(x,y)) is thephase of the complex pupil function. The phase depends on the wavevector k=2π/λ, λ being the wavelength of the individual optical ray,W(x,y) being its path length, and i denotes the imaginary unit number.From the pupil function 74 the point spread function (PSF) 80 can bederived which mathematically can be expressed as a Fourier Transform 82:PSF(x,y)=|FT(P(x,y))|², which is graphically represented as apseudo-three dimensional function 84, depicting a nearlydiffraction-limited case, exhibiting a pseudophakic eye with only minoroptical aberrations. From the calculation 70, the Strehl Ratio i 86 canbe derived which is defined as 88: i=(max(PSF(x,y))/max(PSF_(diff)(x,y)), where PSF(x,y) denotes the point spread function of theaberrated optical system, and PSF_(diff)(x,y) resembles an idealizeddiffraction-limited optical system. The point spread function (PSF) 80and the Strehl Ratio i 86 are useful to visualize the optical quality ofan eye and the clarity of a retinal image.

FIG. 4 is a graphical visualization of the mathematical procedure ofconvolution which can be employed for the purpose of evaluating theclarity of the retinal image. The image formation process 90 can beenvisaged as a mathematical operation—called convolution 94—in which theidealized image of an object 92 is blurred by convolving each imagepoint with the point spread function PSF 96 of the optical systemresulting in an image 100. For the ease of a human eye with a pupil of 6mm diameter, the PSF 96 is depicted as a pseudo-three dimensional graph98. Thus, the clarity of the retinal image 100 can be ascertained by thepoint spread function PSF 96.

FIG. 5 is a side cross-sectional view showing the stress and straindistribution in a loaded cornea as the result of Finite Element Modeling(FEM). By employing a Finite Element Modeling (FEM) algorithm 102 forsimulating the stress 104 and strain 106 distribution throughout aloaded cornea, the local density of the stromal tissue inside the corneacan be determined, from which the spatial distribution of the refractiveindex n (x,y) is derived, yielding a measure of the variability of theoptical path lengths of the manifold of the optical rays inside thecornea. Initially, finite element Modeling (FEM) provides thedistribution of stiffness parameters in the volume elements, which areproportional to local tissue densities. The application of FEM-modelingto cornea biomechanics is described in, e.g., A. Pandolfi, et al.,Biomechan. Model Mechanobiology 5237-246, 2006. An intraocular pressureof 2 kiloPascal (kPA) (15 mm Hg) is applied homogeneously to theposterior surface. Only Bowman's layer 108 is fully fixed at the limbus.On the left part of FIG. 5, a Cauchy stress distribution along theradial direction is depicted; the absolute values range from −2.5 kPa to+2.5 kPa. On the right part of FIG. 5, the maximum principle straindistribution is visualized; the relative compression resp. dilation ofthe stromal tissue range from −0.07 to +0.07.

Use of Fluorescent Emission to Characterize a Cornea

FIG. 6 is a schematic drawing depicting the physical processes of secondharmonic generation imaging (SHGi) and two photon excited fluorescenceimaging (TPEFi). On the upper left side of FIG. 6, the principle ofSecond Harmonic Generation imaging (SHGi) 140 is shown. Two photons 146and 148 with frequency ω_(p) coherently add on to generate a photon 150with frequency 2ω_(p) which is instantaneously reradiated from level 144to 142. In the upper right side of FIG. 6, the Two Photon ExcitedFluorescence imaging (TPEFi) process is visualized. Two photons 156 and158 with frequency ω_(p) excite a molecule from the ground level 152 toan excited level 154. After thermal relaxation to level 160 in about 1picosecond, the fluorescence photon ω_(F) is reradiated, as the moleculeis de-excited to level 162 in about 1 nanosecond. In the lower part ofFIG. 6, the wavelength dependence of the SHGi (Second HarmonicGeneration)- and TPEFi (Two Photon Excited Fluorescence)-imagingprocesses are exemplified. Generally, as the wavelength of theilluminating femtosecond laser beam with frequency ω_(p) is decreasedfrom 166 via 168 to 170, the intensity of the SHGi-signals 174, 176 and178 with frequency 2ω_(p) are increased, as well as the intensities ofthe TPEFi signals 182, 184 and 186 with frequency ω_(F). In the TwoPhoton Cornea Microscope/Opthalmoscope, as described with regard to FIG.7, a wavelength of 780 nm of the illuminating femtosecond laser is used,for optimized contrast of the imaging of collagen fibrils and cellprocesses inside the cornea.

FIG. 7 schematically shows a preferred apparatus 702 for characterizinga cornea for designing a customized intraocular lens. The apparatus 702comprises a laser 704, preferably a two-photon laser, a control unit706, and a scanning unit 708. Two-photon excitation microscopy is afluorescence imaging technique that allows imaging living tissue up to adepth of one millimeter. The two-photon excitation microscope is aspecial variant of the multiphoton fluorescence microscope. Two-photonexcitation can be a superior alternative to confocal microscopy due toits deeper tissue penetration, efficient light detection and reducedphototoxicity. The concept of two-photon excitation is based on the ideathat two photons of low energy can excite a fluorophore in a quantumevent, resulting in the emission of a fluorescence photon, typically ata higher energy than either of the two excitatory photons. Theprobability of the near-simultaneous absorption of two photons isextremely low. Therefore, a high flux of excitation photons is typicallyrequired, usually a femtosecond laser.

A suitable laser is available from Calmar Laser, Inc., Sunnyvale, Calif.Each pulse emitted by the laser can have a duration of from about 50 toabout 100 femtoseconds and an energy level of at least about 0.2 nJ.Preferably the laser 704 generates about 50 million pulses per second ata wavelength of 780 nm, a pulse length of about 50 fs, each pulse havinga pulse energy of about 10 nJ, the laser being a 500 mW laser. Anemitted laser beam 720 is directed by a turning mirror 722 through aneutral density filter 724 to select the pulse energy. The laser beam720 typically has a diameter of about 2 mm when emitted by the laser.The laser beam 720 then travels through a dichroic mirror 728 and thento the scanning unit 708 that spatially distribute the pulses into amanifold of beams. The scanning unit 708 is controlled by a computercontrol system 730 to scan a cornea 732 in an eye.

The beam 720 emitted from the laser has a diameter from about 2 to about2.5 mm. The beam 720, after exiting the scanner 708, is then focused byfocusing means to a size suitable for scanning the cornea 732, typicallya beam having a diameter from about 1 to about 2 μm. The focusing meanscan be any series of lenses and optical devices, such as prisms, thatcan be used for reducing the laser beam to a desired size. The focusingmeans can be a telescopic lens pair 742 and 744 and a microscopeobjective 746, where a second turning mirror 748 directs the beam fromthe lens pair to the microscopic objective. The focusing microscopeobjective can be a 40×/0.8 objective with a working distance of 3.3 mm.The scanning and control unit are preferably a Heidelberg Spectralis HRAscanning unit available from Heidelberg Engineering located inHeidelberg, Germany.

The optics in the scanning unit allow a region having a diameter ofabout 150 to about 450 μm to be scanned without having to move eitherthe cornea 732 or the optics. To scan other regions of the cornea it isnecessary to move the cornea in the x-, y-plane. Also, to scan invarying depths in the cornea, it is necessary to move the focal plane ofthe laser scanner in the z-direction.

The control unit 706 can be any computer that includes storage memory, aprocessor, a display, and input means such as a mouse, and/or keyboard.The control unit is programmed to provide a desired pattern of laserbeams from the scanning unit 708.

The cells on the anterior surface of the cornea 732, when excited by thelaser beam at a wavelength of 780 nm fluoresce, producing a green lighthaving a wavelength of about 530 nm. The emitted light tracks throughthe path of the incident laser light, namely the emitted light passesthrough the microscope objective 746, to be reflected by the turningmirror 748, through the lenses 744 and 742, through the scanning unit708 into the dichroic mirror 728 which reflects the fluorescent light topath 780, generally at a right angle to the path of the incident laserlight that passed through the dichroic mirror 728. In path 780, theemitted light passes through a filter 782 to remove light of unwantedfrequencies, and then through a focusing lens 784 to a photodetector786. The photodetector can be an avalanche photodiode. Data from thephotodetector can be stored in the memory of the computer control unit730, or in other memory.

Thus, the anterior surface of the cornea is illuminated with infraredlight of a wavelength that generates fluorescent light and the generatedfluorescent light is detected. For the anterior surface, incidentinfrared light is focused in a plurality of different planes that aresubstantially perpendicular to the optical axis of the eye, where theplanes intersect the anterior surface of the cornea.

The same procedure can be used for characterizing the posterior surface,by focusing the infrared light in a plurality of different planessubstantially perpendicular to the optical axis of the eye where theplanes intersect the posterior surface. The scanning can be done in 64separate planes, where the scanning is done with beams about threemicrons apart.

A difference for scanning the interior of the cornea is that thecollagen lamellae in the interior region generate blue light rather thangreen light. The blue light has a wavelength of about 390 nm. Whenscanning the interior of the cornea, it is necessary to use a differentfilter 732 to be certain to have the blue light pass through the filterto the photodetector 786.

FIG. 8 is an overview of SHG-imaging of collagen tissue structures. Thecollagen triple helix 188 is visualized in the upper left part of FIG.8, exhibiting the typical structure of collagen fibrils. The collagenfibrils are organized in a complex three dimensional layered structureinside the corneal stroma. On the lower left part of FIG. 8, the SecondHarmonic Generation (SHG) laser/collagen fibril interaction process isdepicted. A photon 194 with the frequency ω polarizes the collagenfibril to an intermediate level 196, whereas a second photon 198 of thesame frequency ω further creates an instantaneous electronic level 192.The electronic excitation is immediately reradiated as a photon 200 ofdouble energy, exhibiting the frequency 2ω. This process occurs withhigh yield because of the unidirectional shape of the collagen fibrils.Second Harmonic Generation imaging (SHGi) of corneal tissue was recentlyreported (M.Han, G. Giese, and J. F. Bille, “Second harmonic generationimaging of collagen fibrils in cornea and sclera”, Opt. Express 13,5791-5795(2005)). The measurement was performed with the apparatus ofFIG. 7. The SHGi signal is determined according to the formulas 224 fromthe nonlinear optical polarization 226 of the collagen fibrils. Thesignal-strength 228 is directly proportional to the second orderpolarization term [χ⁽²⁾]² and inversely proportional to the pulse lengthT of the femtosecond laser pulses. Thus, a SHGi-image of high contrastvisualizes the three dimensional layered structure of the cornealstroma, due to the strong unidirectionality of the collagen fibrils andthe ultrashort pulse length of the femtosecond laser employed in thein-vivo Two Photon Cornea Microscope/Opthalmoscope, as described withregard to FIG. 7.

Anatomically, the cornea 14 of an eye is shown in FIG. 9 to include, inorder from its anterior surface 12 to its posterior surface 16, anepithelium 230, a Bowman's membrane 244, a stroma 246, a Descemet'smembrane 248, and an endothelium 250. The epithelium 230 is comprised ofseveral cell layers, e.g. 232, 234, 236, 238 and 240, merging into thebasal cell layer 242. The basal cell layer 242, as well as the anteriorsurface 12, can clearly be imaged by the two-photon excitedautofluorescence mode (TPEF) of the two-photon cornea microscope,providing a spatially resolved measure of the thickness of theepithelium 230. The endothelium can also be imaged by the two-photonexcited autofluorescence mode of the two-photon cornea microscope,resulting in a spatially resolved thickness measurement of the cornea14. The stroma 246 is composed of approximately 200 collagen lamellae,e.g. 252, 254, 256, 258, 260, 262, and 264, exhibiting a complex threedimensional structure, which can be evaluated utilizing the SecondHarmonic Generation imaging (SHGi) mode of the two-photon corneamicroscope. Based on these measurements, supported by Finite ElementModeling (FEM) of the stiffness of the collagen structure—as exemplifiedin FIG. 5—the three-dimensional distribution of the refractive indexinside the cornea can be reconstructed. Thus, the optical pathlengths—inside the cornea—of the plurality of the optical rays in theray-tracing calculation can be determined with high spatial resolution.Thus the anterior surface, posterior surface and/or internal structureof the cornea can be mapped.

In FIG. 10, the formation of a composite cornea map 270 from individualimaging fields is demonstrated. Typically, a central imaging field 280extends over a diameter of about 2 mm, comprising approximately2000×2000 imaging pixels, which amount to 4 million imaging points orpixels, providing a resolution of approximately 1 μm (e.g. utilizing aNikon 50×/0.45 microscope objective.). The composite cornea map 270contains a three dimensional stack of two-photon microscope images,comprised of either the Two-Photon Excited Fluorescence imaging (TPEFi)-or the Second Harmonic Generation imaging (SHGi)-imaging mode. In orderto match the size of the customized intraocular lens of approximately 6mm diameter, six peripheral imaging fields 290, 292, 294, 296, 298, and300 are employed. The alignment of the individual fields is accomplishedby utilizing a run-time grey value pixel cross correlation algorithm inthe overlap zones 310, 312, 314, 316, 318, and 320. Thus, the compositecornea map exhibits approximately 28 million data, providing a spatiallyresolved composite image of one transversal slice through the cornea.Typically, one hundred transversal slices through the cornea areemployed for reconstructing the optical path lengths of the plurality ofoptical rays as they are transmitted through the cornea of thepseudophakic eye.

Designing and Forming Lenses

Techniques for designing lenses from the data generated by the apparatusof FIG. 7 are known in the art and include the methods described byRoffman in U.S. Pat. No. 5,050,981, which is incorporated herein byreference with regard to such methods. Techniques for manufacturing ormodifying a lens are described in my aforementioned copending U.S.patent application Ser. No. 12/717,886.

Clarity of Vision Determination

With regard to FIG. 11 there is schematically shown a system fordetermining the clarity of vision experienced by a patient, and in theinstance of FIG. 11, with an implanted intraocular lens 1102. The systemused for this is substantially the same as the apparatus shown in FIG. 7using the same laser 704 and scanner 708. Optionally an adaptive-opticsmodule (AO-module) 1104 can be used for the purpose of simulating theeffect of a refractive correction, with regard to image clarity anddepth of focus. The AO-module 708 can be composed of a phase-platecompensator and an active mirror for the purpose of pre-compensatingindividual light beams generated by the laser 704. An adapted opticsdevice to compensate for asymmetric aberrations in a beam of lightuseful for the invention described in my U.S. Pat. No. 7,611,244. Amethod and apparatus for pre-compensating the refractive properties ofthe human with an adaptive optical feedback control is described in myU.S. Pat. No. 6,155,684. Use of active mirrors is described in my U.S.Pat. No. 6,220,707. Individual light beams 1112 pass through the cornea1114 and then the intraocular lens 1102 to be focused on the retina toform a retinal image at 1120. With the incoming light being at awavelength of from about 750 to about 800 nm, preferably about 780 nm,fluorescent proteins in the pigment epithelial cells, as well as thephotoreceptors, emit fluorescent light having a frequency of about 530nm to about 550 nm. The emitted light is represented by lines 1122 inFIG. 11. The intensity of the fluorescent light emitted indicates andcorrelates with how well the cornea 1114 and intraocular lens 1102 focusthe incoming light beams, wherein higher intensity indicates betterfocusing. To determine if improved focusing can be obtained, to increasethe clarity of the image generated by the fluorescent light, the pathlength of the incoming scanning light can be changed, such as byadjusting the phase plate or the active mirror in the adaptive opticsmodule 1104.

Optionally, vision stimulae 1124, such as a Snellen chart can beprovided, to receive subjective feedback from the patient with regard tothe clarity of vision.

Using the method, a prescription for an implanted lens, such as an IOL,corneal lens, or contact lens, as well as modification for an in situlens (cornea, IOL, natural crystalline lens) can be determined.

Although the present invention has been described in considerable detailwith reference to the preferred versions thereof, other versions arepossible. For example, although the present invention is described withregard to use of intraocular lenses, it is understood that the datagenerated characterizing the cornea can be used for forming contactlenses and other lenses implanted in an eye. Therefore the scope of theappended claims should not be limited to the description of thepreferred versions contained therein.

What is claimed is:
 1. A method for generating a map of a cornea of aneye, the cornea having an anterior surface, a posterior surface, and aninterior region between the anterior and posterior surfaces, the methodcomprising the steps of: a) illuminating a portion of the cornea byscanning focused infrared light in a plurality of different planeswithin said portion of the cornea that are substantially perpendicularto an optical axis of the eye, said plurality of planes intersecting thefollowing: i) a first portion of the anterior surface and a firstportion of the posterior surface; and ii) a second portion of theanterior surface, a second portion of the interior region and a firstportion of the posterior surface, and iii) a second portion of theposterior surface and a third portion of the interior region, whereinthe infrared light is of a wavelength that generates fluorescent lightand a Second Harmonic Generation imaging (SHGi) signal by nonlinearoptical processes from the portion of the cornea illuminated; b)detecting and evaluating the fluorescent light and SHGi signal generatedfrom the portion of the cornea illuminated; c) determining the shape ofthe anterior and posterior surfaces and a spatially resolved thicknessmeasurement of the portion of the cornea illuminated from the detectedfluorescent light and the SHGi signal; d) determining from the SHGisignal the three dimensional layered structure of stroma tissue; (e)deriving, using finite element modeling, optical path lengths for theportion of the cornea illuminated from the detected fluorescent lightand SHGi signal; (f) using the derived optical path lengths to generatea map of the anterior surface, posterior surface and the interior regionfor the portion of the cornea illuminated.
 2. The method of claim 1wherein the nonlinear optical processes comprise a Two Photon ExcitedFluorescence imaging (TPEFi) process and the detecting and evaluatingstep comprises detecting any generated green light, wherein the presenceof green light indicates the anterior or posterior surfaces of thecornea.
 3. The method of claim 2 wherein the green light has awavelength of about 530 nanometers.
 4. The method of claim 1 wherein thenonlinear optical processes comprise a Second Harmonic Generationimaging (SHGi) process and the detecting and evaluating step comprisesdetecting any generated blue light, wherein the presence of blue lightindicates the presence of collagen lamellae in the cornea.
 5. The methodof claim 4 wherein the blue light has a wavelength of about 390nanometers.
 6. The method of claim 1 wherein, step f) further includesdetermining a three dimensional distribution of refractive index in theportion of the cornea illuminated from the derived optical path lengthsin the portion of the cornea illuminated.
 7. The method of claim 1wherein the wavelength of the infrared light is about 780 nm.
 8. Themethod of claim 1 wherein the infrared light is emitted as pulses havingan energy level of at least 0.2 nJ.
 9. The method of claim 1 wherein thewavelength of the infrared light is about 750-800 nm.